Interferon Therapy

January 31, 2018 | Author: Anonymous | Category: Science, Health Science, Immunology
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Pharmacology of Interferon

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Interferon

Natural Interferons

Man Made Interferons (Recombinant)

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Interferon Basics • Interferons play an important role in the first line of defense against viral infections • Interferons are part of the non-specific immune system • Interferons are made by cells in response to an appropriate stimulus Downloaded from www.pharmacy123.blogfa.com

Types on Interferon • alpha (leukocyte interferon) – produced by virus infected leukocytes

• beta (fibroblast interferon) – produced by virus infected fibroblasts or epithelial cells

• gamma (immune interferon) – produced by certain activated T cells & NK cells Downloaded from www.pharmacy123.blogfa.com

How Does It Prevent Viral Replication? virus

cells (Other stimuli: exogenous ds RNA, LPS, bacterial components)

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How Does It Prevent Viral Replication? virus interferon

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How Does it Prevent Viral Replication? No replication

virus Inhibitory proteins

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Interferon Response to Acute Viral Infection

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Effects of Interferon Treatment

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Mechanisms of Action • IFN alpha and beta – induction of inhibitory protein synthesis

• IFN gamma – inc class II MHC molecules of APC – Inc ability of macrophages to resist viral infx and kill other cells if infected

• All IFN – inc class I MHC molecules – inc activity ofwww.pharmacy123.blogfa.com NKDownloaded cells from

Viral Defense Against Interferon • block interferon binding to cells • inhibit action of interferon-induced protein kinase • inhibit NK function • interfere with cell surface expression MHC • block complement activation • prevent apoptosis in host cell Downloaded from www.pharmacy123.blogfa.com

Indications for Interferon • alpha – Hepatitis B & C, Hairy cell leukemia, Chronic myeloid leukemia, multiple myeloma, low grade lymphomas, Kaposi’s Sarcoma, Melanoma

• beta – Multiple Sclerosis, (Ulcerative colitis)

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Indications for Interferon • gamma – Chronic granulomatous disease, Chronic Myeloid Leukemia, Renal cell Carcinoma

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Incomplete List of Interferons • • • • • • •

Actimmune Alferon Avonex Betaserone Infergen Intron Wellferon, etc Downloaded from www.pharmacy123.blogfa.com

HCV Epidemiology • HCV is leading cause of liver disease • 4 million Americans have been exposed – approx 3 million are infected

• HCV infection leads to decompensated cirrhosis and hepatocellular carcinoma • HCV-related cirrhosis is the most common reason for OLT in the US NIH Consensus Development Conference Statement 2002 Downloaded from www.pharmacy123.blogfa.com

Distribution of HCV

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Management of Hepatitis C • Consensus Statement in 2002 – treatment eligible patients • IVD users, consume alcohol, comorbidities (depression, HIV coinfections)

– pegylated interferon with ribiviran better than peginterferon monotherapy or standard interferon-ribivarin

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HCV Infection

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Interferon in Hepatitis C • Monotherapy – standard interferon 3 Million units inj tiw (Low Sustained virologic response)

• Combination therapy – standard interferon with ribivarin – pegylated interferon with ribivarin Downloaded from www.pharmacy123.blogfa.com

Interferon in HCV • Limitations – monotherapy not very effective – cumbersome dosing (TIW) – multiple side effects Downloaded from www.pharmacy123.blogfa.com

Interferon Side Effects (Hepatitis C Data)

• • • • • • •

Flu-like symptoms Headache Nausea, vomiting, diarrhea Depression, irritability, anxiety Injection site reactions, partial alopecia Hematologic abnormalities Autoimmune disorders Downloaded from www.pharmacy123.blogfa.com

Management of Side Effects • Depression (77% Manns et al, Lancet 2001) – NIH consensus - “monitor patients for depression and prescribe antidepressants when necessary”

• Hematologic abnormalities – neutropenia and thrombocytopenia • treatment options include decreasing dose or giving hematopoietic growth factors Downloaded from www.pharmacy123.blogfa.com

Pegylated Interferon • HCV is an ideal setting for peginterferon – polyethylene glycol (PEG):interferon

• Pegylation was developed to overcome disadvantages of standard interferon – shields IFN from enzymatic degradation thus lowers systemic clearance – allows less frequent dosing – achieve higher/sustained serum [interferon] Downloaded from www.pharmacy123.blogfa.com

Fried et al: Peginterferon Alfa-2a Plus Ribavirin 56%

60%

44%

50% 40%

29%

monotherapy IFN+RBV Peg+RBV

30% 20% 10% 0% Pega2a

IFN a2b+RBV

Pega2aRBV

P=
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